The effect of anesthetic drugs and techniques on cerebral metabolism and blood flow with particular attention given to either toxic or protective effects continues to be the major thrust of this proposal. If protective effects are suspected, these will be tested in animal models of cerebral ischemia and cerebral hypoxia. Ongoing studies include those dealing with the possible protective effects of barbiturates and hypothermia. Animal models include those complete and incomplete global cerebral ischemia in the dog, incomplete focal cerebral ischemia in primates and cats (middle cerebral artery occlusion) and hypoxia in the mouse. Studies on the effect of anesthetics on CSF production and absorption are underway and are specifically directed at the anesthetic enflurane which has been suggested in previous reports to stimulate metabolic rate in the choroid plexus. The effect of the new anesthetic midazolam on cerebral metabolism and blood flow is also under examination as well as its potential for cerebral protection in the hypoxic mouse models. Because of the observed detrimental effects of prolonged hypothermia and re-warming we are planning studies to examine possible mechanisms of such a detrimental effect and a means by which these can be avoided. Because of the clinical use of prolonged barbiturate therapy, we are examining the effect of tolerance on cerebral metabolism during barbiturate therapy in animals for periods of 24 hours or greater.